Refractory Hydroa Vacciniforme-Like Lymphoma: Biological Insights from Morphoproteomic Analysis

Rohit Goswamy; Helen Ajufo; Abhishek Maiti; Robert Brown; Harinder Juneja; Effrosyni Apostolidou

doi:10.18502/ijhoscr.v16i3.10141

Rohit Goswamy Department of Internal Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas, United States
Helen Ajufo Department of Internal Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas, United States
Abhishek Maiti Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Robert Brown Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas, United States
Harinder Juneja Department of Internal Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas, United States
Effrosyni Apostolidou Department of Internal Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas, United States

DOI: https://doi.org/10.18502/ijhoscr.v16i3.10141

Keywords: Hydroa vacciniforme-like lymphoma (HVLL); Epstein-Barr virus; T-cell lymphoproliferative disorders; Resistance mechanisms; Morphoproteomics

Abstract

T-cell/natural killer cell lymphoproliferative disorders are rare, associated with poor overall survival, and have limited treatment options. We report a case of a patient who developed hydroa vacciniforme-like lymphoma (HVLL, an EBV-peripheral T-cell lymphoma), refractory to multiple lines of systemic therapy including methotrexate, mycophenolate mofetil, dapsone, thalidomide, prednisone, and romidepsin. We conducted morphoproteomic analysis of the patient’s tumor which provided important biological insights. Histopathology showed primarily lymphohistiocytic infiltrates strongly positive EBV expression with a Ki-67 of >50% in the pretreatment biopsy and approximately 90% in the post-treatment biopsy, strong expression of Enhancer of Zester Homolog 2 (EZH2), a constitutively active mTOR pathway, 50% cytoplasmic BCL-2 expression; largely negative PD-1 positive CD8 T-cells. Based on this morphoproteomic analysis and published literature, we postulated that novel agents, including venetoclax, tazemetostat, and other agents may provide a targeted approach for treating HVLL. This case illustrates the use of morphoproteomic analysis to better understand the biology of tumors.